Ketogenic Diet and Ketone Bodies as Clinical Support for the Treatment of SARS-CoV-2—Review of the Evidence

Abstract

One of the proposed nutritional therapies to support drug therapy in COVID-19 is the use of a ketogenic diet (KD) or ketone bodies. In this review, we summarized the evidence from tissue, animal, and human models and looked at the mechanisms of action of KD/ketone bodies against COVID-19. KD/ketone bodies were shown to be effective at the stage of virus entry into the host cell. The use of β-hydroxybutyrate (BHB), by preventing the metabolic reprogramming associated with COVID-19 infection and improving mitochondrial function, reduced glycolysis in CD4+ lymphocytes and improved respiratory chain function, and could provide an alternative carbon source for oxidative phosphorylation (OXPHOS). Through multiple mechanisms, the use of KD/ketone bodies supported the host immune response. In animal models, KD resulted in protection against weight loss and hypoxemia, faster recovery, reduced lung injury, and resulted in better survival of young mice. In humans, KD increased survival, reduced the need for hospitalization for COVID-19, and showed a protective role against metabolic abnormalities after COVID-19. It appears that the use of KD and ketone bodies may be considered as a clinical nutritional intervention to assist in the treatment of COVID-19, despite the fact that numerous studies indicate that SARS-CoV-2 infection alone may induce ketoacidosis. However, the use of such an intervention requires strong scientific validation.

Uncovering the Effect of SARS-CoV-2 on Liver Metabolism via Genome-Scale Metabolic Modeling for Reprogramming and Therapeutic Strategies

“…Several studies in the literature demonstrated that the supplements used in this study like dopamine, glucosamine, D -xylose, cysteine, ( R )-3-hydroxybutanoate, lovastatin, and simvastatin have the potential to develop therapeutic strategies to fight SARS-CoV-2. − Dopamine is an important neurotransmitter and required for proper functioning of the body including movement, memory, and motivation. Administration of dopamine reduced the viral replication in CaLu-3 human lung epithelial cells and virus-based cytopathic effect in Vero E6 epithelial cells infected with SARS-CoV-2. , Glucosamine is a common dietary supplement that promotes joint health.…”

“…N -acetylcysteine was proposed as both in potential treatment and prevention against SARS-CoV-2 in different studies. − ( R )-3-hydroxybutanoate is a ketone body that provides an alternative carbon source for the cellular metabolism. Ketogenic diet is recommended as nutritional therapy for the treatment of COVID-19 by restoring perturbed energy metabolism and redox state. − Lovastatin and simvastatin are lipid-lowering medications and belong to the statin class exhibiting anti-inflammatory, antithrombotic, and immunomodulatory features . Lovastatin administration in COVID-19 patients led to a significant decrease in the duration of hospitalization in intensive care unit .…”

Very low-calorie ketogenic diet (VLCKD) in the management of hidradenitis suppurativa (Acne Inversa): an effective and safe tool for improvement of the clinical severity of disease. Results of a pilot study

“…These compounds are believed to have the potential to counteract inflammation and provide antioxidant effects within the body [ 58 ]. This, in turn, could potentially reduce the occurrence of age-related diseases and viral infections like COVID-19 [ 59 , 60 ]. However, the exact molecular mechanisms responsible for how ketone bodies alleviate oxidative stress and inflammation remain a topic of ongoing investigation.…”

COVID-19 and Gastrointestinal Tract: From Pathophysiology to Clinical Manifestations

“…Clinical trials using dietary modification, probiotics, prebiotics, and fecal microbiota transplantation are underway to determine their effectiveness in the treatment of acute COVID-19 and possibly enhance the effectiveness of SARS-CoV-2 vaccines [152][153][154][155][156][157][158]. Only long-term clinical data and future research shall provide better insight into the complex bidirectional interaction between the virus and the alimentary tract in healthy patients and those with preexisting gastrointestinal diseases.…”